PROJECT SUMMARY/ABSTRACT Dr. Yu, an adult cardiologist at Memorial Sloan Kettering (MSK) with advanced training in echocardiography, has demonstrated a strong commitment to developing a career as a clinical investigator in cardio-oncology. His long-term goal is to lead efforts to develop evidence-based strategies for the prevention, detection, and management of cancer therapy-associated cardiotoxicity in order to mitigate the competing cardiovascular causes of morbidity and mortality in cancer survivors. The career development and training plans outlined in this application have been tailored to provide Dr. Yu with the necessary skills, structured mentoring, and research experience to meet his long-term research and career goals and ensure a successful transition to independence as a clinician scientist. Members of a multidisciplinary mentorship team comprised of nationally recognized leaders in survivorship, cardio-oncology, and health outcomes are committed to providing close supervision and guidance to Dr. Yu in achieving all of the career development, training, and research objectives of this proposal. The overall objective of the scientific aspect of this proposal is to better understand the harms and benefits associated with cardiac monitoring during trastuzumab therapy. Cardiotoxicity is a well recognized adverse effect of trastuzumab therapy used to treat HER2-positive breast cancer. Clinical guidelines for cardiac monitoring during trastuzumab therapy recommend routine serial assessments of left ventricular ejection fraction (LVEF). However, evidence to support this one-size-fits-all recommendation for all patients treated with trastuzumab is lacking, particularly given the growing trend in the use of non-anthracycline trastuzumab-based regimens with safer cardiotoxicity risk profiles. There is also the potential harm that false- positive results or clinically insignificant LVEF declines detected during routine cardiac monitoring will unnecessarily lead to interruption or early termination of curative and life-saving breast cancer therapy and result in worse cancer outcomes. The central hypothesis is that a strategy of limited cardiac monitoring among women with a low cardiovascular risk profile and treated with a non-anthracycline trastuzumab-based regimen will be safe and less costly. Dr. Yu will address this central hypothesis using two distinct and complementary approaches. In Aim 1, he will capitalize on existing variations in the frequency of cardiac monitoring observed at MSK to retrospectively examine the association between adherence to cardiac monitoring guidelines and cardiotoxicity events. In Aim 2, acknowledging the limitations of a retrospective study design, he will prospectively evaluate the safety and feasibility of a limited cardiac monitoring strategy in patients treated with a non-anthracycline trastuzumab-based regimen. In Aim 3, he will estimate the healthcare utilization and costs associated with guideline-based versus limited cardiac monitoring strategies. The knowledge gained on the harms and benefits of cardiac monitoring will lay the groundwork to develop evidence-based recommendations for cardiac monitoring during breast cancer therapy.